The hippocampus, a structure in the medial temporal lobe, plays a critical role in memory. Damage to the hippocampus resulting from ischemia, epilepsy, or Alzheimer's disease produces profound and often debilitating memory deficits; however, the processes underlying memory formation in the hippocampus are not well understood. The central objective of this proposal is to improve our understanding of these mechanisms. Such knowledge may lead to novel methods for early detection of hippocampal malfunction, which would ensure that available therapies are maximally effective. The role of the hippocampus in recognition memory is currently a matter of significant controversy. Although damage to the hippocampus in humans produces severe recognition memory deficits, findings in monkeys have been inconsistent. While some studies have found impairment in recognition memory following lesions of the hippocampus, other studies have reported no impairment. To further complicate the matter, physiological studies in monkeys have provided little evidence for the existence of recognition memory signals in the hippocampus, despite the existence of such signals in surrounding cortical areas. The experiments in this proposal are aimed at resolving this controversy by investigating neural signals in the monkey hippocampus using behavioral tasks which are new to physiological studies. One of these tasks, the Visual Preferential Looking Task is known to be especially sensitive to hippocampal damage in both monkeys and humans. Our preliminary data indicate that modulations in the firing rate of hippocampal neurons and the amplitude of hippocampal local field potentials reflect the relative familiarity of visual stimuli. In addition, our results indicate that an increase in temporally correlated activity across the hippocampus, i.e., neuronal synchronization, during encoding predicts the strength of subsequent recognition. These approaches have not been used previously to study memory in the medial temporal lobe. Accordingly, this project has the potential to reveal previously unknown neuronal mechanisms underlying memory formation. Findings from this study could be used to develop new criteria for identifying aberrant neural activity in humans exhibiting symptoms of memory loss, including patients with Mild Cognitive Impairment, who are at an increased risk of developing Alzheimer's Disease. This study would provide a basis for noninvasive studies in human patients examining neural activity in the hippocampus during memory formation. The possibility that a disruption in neuronal synchrony may underlie the memory impairment in these patients also suggests that therapies aimed at aleviating this disruption could be used to treat memory loss. [unreadable] [unreadable] [unreadable]